Process for the preparation of 1-(pyrimidin-2-yl) Propan-2-ones

ABSTRACT

A process for the preparation of 1-(pyrimidin-2-yl)propan-2-ones of general formula (I), in which R is in each case a C 1-10 -alkyl group, a C 3-8 -cycloalkyl group, an alkyl group or an aryl-C 1-4 -alkyl group. For this, a malondiimidate of the general formula (II), in which R has the meaning given above, is reacted with diketene. The compounds which can be prepared according to the invention are intermediates for the synthesis of agrochemical active ingredients.

[0001] The invention relates to a process for the preparation of1-(pyrimidin-2-yl)propan-2-ones of the general formula

[0002] in which R is in each case a C₁₋₁₀-alkyl group, a C₃₋₈-cycloalkylgroup, an ally group or an aryl-C₁₋₄-alkyl group. C₁₋₁₀-Alkyl groups areunderstood here and below as meaning all linear or branched primary,secondary or tertiary alkyl groups having 1 to 10 carbon atoms, thus,for example, methyl, ethyl propyl, isopropyl, butyl, isobutyl sec-butyl,tert-butyl, pentyl isopentyl, tert-pentyl, neopentyl hexyl, heptyl,octyl, nonyl or decyl.

[0003] C₃₋₈-Cycloalkyl are to be understood as meaning, in particular,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl andcyclooctyl.

[0004] Aryl-C₁₋₄-alkyl groups are the groups composed of an aryl groupand an alkyl group having 1 to 4 carbon atoms, aryl groups beingunderstood as meaning, in particular, phenyl or naphthyl groups. Thearyl groups may also be substituted by one or more C₁₋₄-alkyl groups,C₁₋₄-alkoxy groups or halogen atoms. Examples of aryl-C₁₋₄-alkyl groupsare, in particular, benzyl, 1-phenylethyl, 2-phenylethyl and3-phenylpropyl.

[0005] Compounds of the formula I, in particular the dimethoxy compound(R=Me) are potential intermediates in the synthesis of agrochemicalactive ingredients.

[0006] Syntheses of these compounds have hitherto not been described inthe prior art.

[0007] It was an object of the present invention to provide apreparation process which is simple and suitable for an industrialscale.

[0008] According to the invention, the object is achieved by the processof Claim 1. It has been found that the malondiimidates, which arereadily available from malodinitrile and the corresponding alcohols(DE-A-24 26 913, EP-A0 024 200), of the general formula

[0009] in which R has the meaning given above, react with diketene ofthe formula

[0010] directly and in a good yield to give the desired compounds (I).

[0011] The malondiimidates (II) can either be used without a diluent (asfree base) or else be formed in situ from a corresponding salt and abase. The latter may be an inorganic base or an organic base such as atertiary amine. The malondiimidates are preferably used without adiluent. For this, they can, for example, be extracted with a solvent oflow polarity, such as dichloromethane or diethyl ether, from aneutralized solution of one of their salts and be isolated byevaporating the solvent (EP-A0 024 200).

[0012] The salts of the malondiimidates (II) used are preferably thedihydrochlorides.

[0013] The process according to the invention is preferably used for thepreparation of 1-(4,6-dimethoxypyrimidin-2-yl)propan-2-ones, by usingdimethyl malondiimidate (R=Me) as malondiimidate (II).

[0014] The process according to the invention is advantageously carriedout in a solvent which is essentially inert under the reactionconditions, such as, for example, aromatic hydrocarbons like toluene orxylene or ketones like acetone. The reaction temperature isadvantageously 50 to 150° C. for the aromatic solvents or 0 to 100° C.for ketone solvents.

[0015] The examples below illustrate how the process according to theinvention is carried out, but are not intended to impose any limitation.

EXAMPLE 1 1-(4,6-Dimethoxypyrimidin-2-yl)propan-2-one

[0016] A solution of dimethyl malondiimidate (80 g, 0.61 mol) in toluene(240 ml) was heated to 80° C. Diketene (103.44 g, 1.23 mmol) was addedover the course of 2 h, the temperature being held at 80° C. Thereaction mixture was held at 80° C. for a further 2 h and then cooled toroom temperature. Following the addition of water (200 ml), it wasstirred for 0.5 h and then the phases were separated. The aqueous phasewas extracted with toluene (590 ml) and the combined organic phases weredried over sodium sulfate. Filtration and evaporation of the solvent invacuo gave 117.3 g of crude product in the form of a reddish liquid. Thecrude product was purified by distillation on a 20 cm Vigreux column.

[0017] Yield: 61.29 g, purity (GC)>98% (55% of theory, based on dimethylmalondiimidate). B.p.: 90° C./0.4 mbar ¹H NMR (CDCl₃): δ=5.92 (s, 1H);3.91 (s, 6H); 3.86 (s, 2H); 2.27 (s, 3H). In addition, the spectrum alsohas the signals of the enol form.

EXAMPLE 2 1-(4,6-Dimethoxypyrimidin-2-yl)propan-2one

[0018] Dimethyl malondiimidate dihydrochloride (90.0 kg, 443 mol, 1 eq)and acetone (330 l) were placed under nitrogen in a 630 l stirredvessel. The suspension was cooled to 0 to 5° C. and triethylamine (98.7k, 975 mol, 2.2 eq) was added over the course of 120 min at 0 to 5° C.The suspension was stirred for another 30 min at 0 to 5° C. and thenwarmed to 25° C. Diketene (44.7 kg, 531 mol. 1.2 eq) was added within 90min at ca. 25° C. After the addition the mixture was heated to 30° C.and after 2 h reaction time at the same temperature the excess diketenewas destroyed by adding methanol (15 l) and 4-(dimethylamino)pyridine(0.5 kg). The precipitated trimethylammonium chloride (ca. 160 kg) wasfiltered off and the filter cake was washed with acetone (2×113 l). Thecombined filtrates were concentrated by distilling off acetone (450-500l) at ambient pressure. The residual solution was cooled to 40° C. andwater (198 l) was added. In order to remove the acetone completely, thesolution was subjected to another distillation at 100 to 200 mbar untila head temperature of ca. 45° C. had been reached (after ca. 5 h) and ca150-180 l of distillate had been obtained. The residue was cooled to 30°C., seeded by adding 1-(4,6-dimethoxypyrimidin-2-yl)propan-2-onecrystals (0.6 kg) and subsequently cooled to 0° C. within 60 min. Afteranother 60 min at 0° C. the product was filtered, washed with cold water(135 l) and dried at 35° C./<100 mbar (16 h).

[0019] Yield: 49 kg (55%) slightly yellowish solid, purity >95%.

1. A process for the preparation of a 1-(Pyrimidin-2-yl)propan-2-one ofthe formula:

in which R is in each case a C₁₋₁₀-alkyl group, a C₃₋₈-cycloalkyl group,an allyl group or an aryl-C₁₋₄-alkyl group, comprising reacting amalondiimidate of the formula:

in which R has the meaning given above, with diketene of the formula:


2. The process according to claim 1, wherein the malondiimidate (II) isprepared in situ from a corresponding salt and a base.
 3. The processaccording to claim 2, wherein the salt of the malondiimidate (II) usedis the dihydrochloride.
 4. The process according to claim 3, wherein thebase is a tertiary amine.
 5. The process according to claim 4, whereinthe malondiimidate (II) used is dimethyl malondiimidate.
 6. The processaccording to claim 2, wherein the base is a tertiary amine.
 7. Theprocess according to claim 4, wherein the malondiimidate (ii) used isdimethyl malondiimidate.
 8. The process according to claim 5 wherein, inthe compounds of formulae (I) and (II), R in each case is methyl.
 9. Theprocess according to claim 1, wherein the reaction is carried out in asolvent that is essentially inert under reaction conditions.
 10. Theprocess according to claim 9, wherein the solvent is an aromatichydrocarbon or a ketone.